Depression is an affectivity disorder, in which a depressive syndrome predominates, depressive being associated with a low feeling or denoting a sad disposition. The anti-depressants used for therapy are also important adjuvants for pain therapy (in Analgesics—from Chemistry and Pharmacology to Clinical Application, 265-284, Wiley VCH, 2002), in particular for chronic pain, as the prolonged stress of pain may lead to a depressive mood in the patient. This is often the case with patients suffering from pain with cancer (Berard, Int. Med. J. 1996, 3/4 257-259). As there have previously been no painkillers with a clinically relevant anti-depressive active component, the anti-depressants have to be added as a medication supplementary to the analgesic dose. As patients with chronic pain frequently require a large number of different medicines, the additional dose of the anti-depressant leads to further stressing of the organism. For this reason and to increase acceptance, an analgesically effective substance with an anti-depressive active component would be particularly advantageous.
The basis of the anti-depressive efficacy is the reuptake inhibition of serotonin.
Various derivatives from the structural class of 3-pyrrolidine-indoles are already known from the literature.
WO9311106 describes 5-substituted 3-pyrrolidine-indole derivatives, wherein the radical on the pyrrolidine nitrogen represents an alkyl chain or aryl.
WO02051837 describes 3-pyrrolidine-indole derivatives as 5-HT6 ligands, wherein the radical on the pyrrolidine nitrogen represents an alkyl chain, in which one carbon may also be replaced by oxygen or nitrogen, cycloalkyl, cycloheteroaryl, aryl or heteroaryl.
WO9410171 discloses 3-pyrrolidine-indole derivatives with alkyl, aryl and alkyl aryl as nitrogen substituents of the pyrrolidine as analgesically effective compounds which, however, are substituted in the 5 position.
U.S. Pat. No. 3,109,844 discloses 3-pyrrolidine-indole derivatives which carry a substituted alkyl radical on the pyrrolidine nitrogen.
WO02079190 describes 3-pyrrolidine-indole derivatives which carry a specifically substituted alkyl radical (a saturated nitrogen heterocycle) on the pyrrolidine nitrogen. These 3-pyrrolidine-indole derivatives are chemokine antagonists.
WO02079151 describes 3-pyrrolidine-indole derivatives which have an alkyl chain on the pyrrolidine nitrogen, which may be interrupted by a cyclic radical, these derivatives being chemokine antagonists.
WO0214317 discloses 3-pyrrolidine-indole derivatives, wherein a pyrazole radical is linked via an alkyl chain, which chain may also contain heteroatoms, to the pyrrolidine nitrogen.
WO0143740 discloses 3-pyrrolidine-indole derivatives, wherein an aryl radical is linked via an alkyl chain, which is interrupted by a heteroatom, to the pyrrolidine nitrogen.
WO9958525 and WO9910346 disclose 3-pyrrolidine-indole derivatives, wherein a dihydroindole radical or 3,4-dihydro-1H-benzo[1,2,6]thiadiazine-2,2-dioxide is linked via an alkyl chain to the pyrrolidine nitrogen.
U.S. Pat. No. 5,891,875 describes 3-pyrrolidine-indole derivatives, wherein a substituted morpholine radical is linked via a methylcarbonyl group to the pyrrolidine nitrogen.
U.S. Pat. No. 5,792,760 discloses 3-pyrrolidine-indole derivatives, wherein a N-benzyl-N-(3-1H-indol-3-yl-propionyl)-acetamide radical is linked via an ethylamine group to the pyrrolidine nitrogen.
WO9740038 discloses compounds, wherein the pyrrolidine nitrogen is linked to an alkyl chain or a cycloalkyl ring, a phenyl radical or a nitrogen substituent via an alkylamine chain, an alkylamide chain or an amide function.
The majority of compounds listed are described as serotonin receptor ligands or serotonin reuptake inhibitors.